Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Gill, J. H.
Right arrow Articles by Roberts, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gill, J. H.
Right arrow Articles by Roberts, R. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis, Vol 19, 1743-1747, Copyright © 1998 by Oxford University Press

ARTICLES

The rodent non-genotoxic hepatocarcinogen nafenopin suppresses apoptosis preferentially in non-cycling hepatocytes but also elevates CDK4, a cell cycle progression factor

JH Gill, P Brickell, C Dive and RA Roberts
Molecular Pharmacology Group, School of Biological Sciences, Manchester University, UK.

Rodent non-genotoxic hepatocarcinogens such as nafenopin suppress spontaneous and transforming growth factor beta1 (TGFbeta1)-induced rat hepatocyte apoptosis as well as inducing DNA synthesis. We wished to determine if these two processes are associated. In primary rat hepatocytes, nafenopin suppressed apoptosis from 1.9 to 0.63% but more apoptotic bodies were bromodeoxyuridine (BrdU)-labelled (0.35%) than predicted statistically from a random distribution of apoptosis within the cycling and non-cycling populations (0.10%). In contrast, TGFbeta1 induced hepatocyte apoptosis (7.8%) but fewer hepatocytes were BrdU- labelled (0.29%) than predicted (0.82%). Western blot analyses showed that nafenopin and TGFbeta1 had opposing effects on cyclin-dependent kinase 4 (CDK4) protein: nafenopin elevated CDK4 compared with controls, whereas TGFbeta1 caused a reduction. These data suggest that non-genotoxic hepatocarcinogens suppress apoptosis in the non-cycling population of hepatocytes and elevate CDK4 levels, possibly allowing potentially tumourigenic cells to enter the cell cycle.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
R. A. Canuto, G. Muzio, M. Maggiora, A. Trombetta, G. Martinasso, R. Autelli, P. Costelli, G. Bonelli, and F. M. Baccino
Apoptosis induced by clofibrate in Yoshida AH-130 hepatoma cells: role of HMG-CoA reductase
J. Lipid Res., January 1, 2003; 44(1): 56 - 64.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. Chevalier and R.A. Roberts
G1-arrested FaO cells re-enter the cell cycle upon stimulation with the rodent non-genotoxic hepatocarcinogen nafenopin
Carcinogenesis, July 1, 1999; 20(7): 1209 - 1213.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S Chevalier, N Macdonald, and R. Roberts
Induction of DNA replication by peroxisome proliferators is independent of both tumour necrosis factor (alpha) priming and EGF-receptor tyrosine kinase activity
J. Cell Sci., January 12, 1999; 112(24): 4785 - 4791.
[Abstract] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.